tbuckley/cabot-search huggingface dataset:
Dual-crosslinked regenerative hydrogel for sutureless long-term repair of corneal defect
Authors: Xuanren Shen, Saiqun Li, Xuan Zhao, Jiandong Han, Jiaxin Chen, Zilong Rao, Kexin Zhang, Daping Quan, Jin Yuan, Ying Bai
Journal: Bioactive Materials (2022)

Corneal transplantation is the most effective clinical treatment for corneal defects, but it requires precise size of donor corneas, surgical sutures, and overcoming other technical challenges. Postoperative patients may suffer graft rejection and complications caused by sutures. Ophthalmic glues that can long-term integrate with the corneal tissue and effectively repair the focal corneal damage are highly desirable. Herein, a hybrid hydrogel consisting of porcine decellularized corneal stroma matrix (pDCSM) and methacrylated hyaluronic acid (HAMA) was developed through a non-competitive dual-crosslinking process. It can be directly filled into corneal defects with various shapes. More importantly, through formation of interpenetrating network and stable amide bonds between the hydrogel and adjacent tissue, the hydrogel manifested excellent adhesion properties to achieve suture-free repair. Meanwhile, the hybrid hydrogel not only preserved bioactive components from pDCSM, but also exhibited cornea-matching transparency, low swelling ratio, slow degradation, and enhanced mechanical properties, which was capable of withstanding superhigh intraocular pressure. The combinatorial hydrogel greatly improved the poor cell adhesion performance of HAMA, supported the viability, proliferation of corneal cells, and preservation of keratocyte phenotype. In a rabbit corneal stromal defect model, the experimental eyes treated with the hybrid hydrogel remained transparent and adhered intimately to the stroma bed with long-term retention, accelerated corneal re-epithelialization and wound healing. Giving the advantages of high bioactivity, low-cost, and good practicality, the dual-crosslinked hybrid hydrogel served effectively for long-term suture-free treatment and tissue regeneration after corneal defect.
The Transposition Rate Has Little Influence on the Plateauing Level of the P-element
Authors: Robert Kofler, Viola Nolte, Christian Schlötterer
Journal: Molecular Biology and Evolution (2022)

The popular trap model assumes that the invasions of transposable elements (TEs) in mammals and invertebrates are stopped by piRNAs that emerge after insertion of the TE into a piRNA cluster. It remains, however, still unclear which factors influence the dynamics of TE invasions. The activity of the TE (i.e., transposition rate) is one frequently discussed key factor. Here we take advantage of the temperature-dependent activity of the P-element, a widely studied eukaryotic TE, to test how TE activity affects the dynamics of a TE invasion. We monitored P-element invasion dynamics in experimental Drosophila simulans populations at hot and cold culture conditions. Despite marked differences in transposition rates, the P-element reached very similar copy numbers at both temperatures. The reduction of the insertion rate upon approaching the copy number plateau was accompanied by similar amounts of piRNAs against the P-element at both temperatures. Nevertheless, we also observed fewer P-element insertions in piRNA clusters than expected, which is not compatible with a simple trap model. The ping-pong cycle, which degrades TE transcripts, becomes typically active after the copy number plateaued. We generated a model, with few parameters, that largely captures the observed invasion dynamics. We conclude that the transposition rate has at the most only a minor influence on TE abundance, but other factors, such as paramutations or selection against TE insertions are shaping the TE composition.
Re: Börje Ljungberg, Laurence Albiges, Yasmin Abu-Ghanem, et al. European Association of Urology Guidelines on Renal Cell Carcinoma: The 2022 Update. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2022.03.006
Authors: Yongbao Wei, Ruochen Zhang, Le Lin
Journal: European Urology (2022)
Dispensing of Oral Antiviral Drugs for Treatment of COVID-19 by Zip Code–Level Social Vulnerability — United States, December 23, 2021–May 21, 2022
Authors: Jeremy A.W. Gold, James Kelleher, Jake Magid, Brendan R. Jackson, Meghan E. Pennini, Diana Kushner, Emily J. Weston, Bobby Rasulnia, Sachiko Kuwabara, Kelly Bennett, Barbara E. Mahon, Anita Patel, John Auerbach
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

The COVID-19 pandemic has highlighted and exacerbated long-standing inequities in the social determinants of health (1-3). Ensuring equitable access to effective COVID-19 therapies is essential to reducing health disparities. Molnupiravir (Lagevrio) and nirmatrelvir/ritonavir (Paxlovid) are oral antiviral agents effective at preventing hospitalization and death in patients with mild to moderate COVID-19 who are at high risk* for progression to severe COVID-19 when initiated within 5 days of symptom onset. These medications received Emergency Use Authorization from the Food and Drug Administration (FDA) in December 2021† and were made available at no cost to recipients through the U.S. Department of Health and Human Services (HHS) on December 23, 2021. Beginning March 7, 2022, a series of strategies was implemented to expand COVID-19 oral antiviral access, including the launch of the Test to Treat initiative.§ Data from December 23, 2021-May 21, 2022, were analyzed to describe oral antiviral prescription dispensing overall and by week, stratified by zip code social vulnerability. Zip codes represented areas classified as low, medium, or high social vulnerability; approximately 20% of U.S. residents live in low-, 31% in medium-, and 49% in high-social vulnerability zip codes.¶ During December 23, 2021-May 21, 2022, a total of 1,076,762 oral antiviral prescriptions were dispensed (Lagevrio = 248,838; Paxlovid = 827,924). Most (70.3%) oral antivirals were dispensed during March 7-May 21, 2022. During March 6, 2022-May 21, 2022, the number of oral antivirals dispensed per 100,000 population increased from 3.3 to 77.4 in low-, from 4.5 to 70.0 in medium-, and from 7.8 to 35.7 in high-vulnerability zip codes. The number of oral antivirals dispensed rose substantially during the overall study period, coincident with the onset of initiatives to increase access. However, by the end of the study period, dispensing rates in high-vulnerability zip codes were approximately one half the rates in medium- and low-vulnerability zip codes. Additional public health, regulatory, and policy efforts might help decrease barriers to oral antiviral access, particularly in communities with high social vulnerability.
Overlooking a More Typical Culprit—Reply
Authors: Guofeng Wang, Qinghua Chang, Yuanzhe Jin
Journal: JAMA Internal Medicine (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
NOD/RIPK2 signalling pathway contributes to osteoarthritis susceptibility
Authors: Michael J Jurynec, Catherine M Gavile, Matthew Honeggar, Ying Ma, Shivakumar R Veerabhadraiah, Kendra A Novak, Kazuyuki Hoshijima, Nikolas H Kazmers, David J Grunwald
Journal: Annals of the Rheumatic Diseases (2022)

How inflammatory signalling contributes to osteoarthritis (OA) susceptibility is undetermined. An allele encoding a hyperactive form of the Receptor Interacting Protein Kinase 2 (RIPK2) proinflammatory signalling intermediate has been associated with familial OA. To test whether altered nucleotide-binding oligomerisation domain (NOD)/RIPK2 pathway activity causes heightened OA susceptibility, we investigated whether variants affecting additional pathway components are associated with familial OA. To determine whether the Ripk2104Asp disease allele is sufficient to account for the familial phenotype, we determined the effect of the allele on mice.Genomic analysis of 150 independent families with dominant inheritance of OA affecting diverse joints was used to identify coding variants that segregated strictly with occurrence of OA. Genome editing was used to introduce the OA-associated RIPK2 (p.Asn104Asp) allele into the genome of inbred mice. The consequences of the Ripk2104Asp disease allele on physiology and OA susceptibility in mice were measured by histology, immunohistochemistry, serum cytokine levels and gene expression.We identified six novel variants affecting components of the NOD/RIPK2 inflammatory signalling pathway that are associated with familial OA affecting the hand, shoulder or foot. The Ripk2104Asp allele acts dominantly to alter basal physiology and response to trauma in the mouse knee. Whereas the knees of uninjured Ripk2Asp104 mice appear normal histologically, the joints exhibit a set of marked gene expression changes reminiscent of overt OA. Although the Ripk2104Asp mice lack evidence of chronically elevated systemic inflammation, they do exhibit significantly increased susceptibility to post-traumatic OA (PTOA).Two types of data support the hypothesis that altered NOD/RIPK2 signalling confers susceptibility to OA.
Phase I study of adjuvant immunotherapy with autologous tumor-infiltrating lymphocytes in locally advanced cervical cancer
Authors: He Huang, Cai-ping Nie, Xiu-feng Liu, Bin Song, Jian-hui Yue, Jing-xiao Xu, Jia He, Kui Li, Yan-ling Feng, Ting Wan, Min Zheng, Yan-Na Zhang, Wei-Jun Ye, Jun-Dong Li, Yan-Fang Li, Jun-yun Li, Xin-Ping Cao, Zhi-min Liu, Xiao-shi Zhang, Qing Liu, Xi Zhang, Ji-Hong Liu, Jiang Li
Journal: Journal of Clinical Investigation (2022)

BACKGROUND. Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs) has achieved remarkable clinical efficacy in metastatic cancers such as melanoma and cervical cancer (CC). Here, we explored the safety, feasibility, and preliminary tumor response and performed translational investigations of adjuvant immunotherapy using infusion of autogenous TILs (auto-TILs) following concurrent chemoradiotherapy (CCRT) in patients with CC who had locally advanced disease.
Lenalidomide plus R-GDP (R2-GDP) in Relapsed/Refractory Diffuse Large B-Cell Lymphoma: Final Results of the R2-GDP-GOTEL Trial and Immune Biomarker Subanalysis
Authors: Natalia Palazón-Carrión, Alejandro Martín García-Sancho, Esteban Nogales-Fernández, Carlos Jiménez-Cortegana, Fernando Carnicero-González, Eduardo Ríos-Herranz, Fátima de la Cruz-Vicente, Guillermo Rodríguez-García, Rubén Fernández-Álvarez, Natividad Martínez-Banaclocha, Josep Gumà-Padrò, José Gómez-Codina, Antonio Salar-Silvestre, Delvys Rodríguez-Abreu, Laura Gálvez-Carvajal, Jorge Labrador, María Guirado-Risueño, Daniel J. García-Domínguez, Lourdes Hontecillas-Prieto, Pablo Espejo-García, Isabel Fernández-Román, Mariano Provencio-Pulla, Margarita Sánchez-Beato, Marta Navarro, Lejeune Marylene, Tomás Álvaro-Naranjo, Maria Casanova-Espinosa, Victor Sánchez-Margalet, Antonio Rueda-Domínguez, Luis de la Cruz-Merino
Journal: Clinical Cancer Research (2022)

Abstract Purpose: New therapeutic options are needed in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Lenalidomide-based schedules can reverse rituximab refractoriness in lymphoma. Patients and Methods: In the phase II R2-GDP trial, 78 patients unsuitable for autologous stem cell transplant received treatment with the following schedule: lenalidomide 10 mg Days (D)1–14, rituximab 375 mg/m2 D1, cisplatin 60 mg/m2 D1, gemcitabine 750 mg/m2 D1 and D8, and dexamethasone 20 mg D1–3, up to 6 cycles (induction phase), followed by lenalidomide 10 mg (or last lenalidomide dose received) D1–21 every 28 days (maintenance phase). Primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, and monitorization of key circulating immune biomarkers (EU Clinical Trials Register number: EudraCT 2014-001620-29). Results: After a median follow-up of 37 months, ORR was 60.2% [37.1% complete responses (CR) and 23.1% partial responses (PR)]. Median OS was 12 months (47 vs. 6 months in CR vs. no CR); median PFS was 9 months (34 vs. 5 months in CR vs. no CR). In the primary refractory population, ORR was 45.5% (21.2% CR and 24.3% PR). Most common grade 3–4 adverse events were thrombocytopenia (60.2%), neutropenia (60.2%), anemia (26.9%), infections (15.3%), and febrile neutropenia (14.1%). Complete responses were associated with a sharp decrease in circulating myeloid-derived suppressor cells and regulatory T cells. Conclusions: R2-GDP schedule is feasible and highly active in R/R DLBCL, including the primary refractory population. Immune biomarkers showed differences in responders versus progressors.
Robotic Radical Prostatectomy for Prostate Cancer in Renal Transplant Recipients: Results from a Multicenter Series
Authors: Giancarlo Marra, Marco Agnello, Andrea Giordano, Francesco Soria, Marco Oderda, Charles Dariane, Marc-Olivier Timsit, Julien Branchereau, Oussama Hedli, Benoit Mesnard, Derya Tilki, Jonathon Olsburgh, Meghana Kulkarni, Veeru Kasivisvanathan, Alberto Breda, Luigi Biancone, Paolo Gontero
Journal: European Urology (2022)
Biomarkers of Airway Immune Homeostasis Differ Significantly with Generation of E-Cigarettes
Authors: Elise Hickman, Alexis Payton, Parker Duffney, Heather Wells, Agathe S. Ceppe, Stephanie Brocke, Aleah Bailey, Meghan E. Rebuli, Carole Robinette, Brian Ring, Julia E. Rager, Neil E. Alexis, Ilona Jaspers
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Numerous studies have demonstrated that e-cigarettes can impact respiratory immune homeostasis; however, the extent of these effects remains an active area of investigation, and most previous studies were conducted with model systems or subjects exposed to third-generation e-cigarettes, such as vape pens and box mods.
Elicitation of pneumovirus-specific B cell responses by a prefusion-stabilized respiratory syncytial virus F subunit vaccine
Authors: Emily Phung, Lauren A. Chang, Maryam Mukhamedova, Lijuan Yang, Deepika Nair, Scott A. Rush, Kaitlyn M. Morabito, Jason S. McLellan, Ursula J. Buchholz, John R. Mascola, Michelle C. Crank, Grace Chen, Barney S. Graham, Tracy J. Ruckwardt
Journal: Science Translational Medicine (2022)

Respiratory syncytial virus (RSV) is a substantial cause of morbidity and mortality globally. A candidate RSV prefusion (pre-F)-stabilized subunit vaccine, DS-Cav1, has previously been shown to elicit potent and durable neutralizing activity in a phase 1 clinical trial in healthy adults. Here, we used fluorescently labeled probes and flow cytometry to evaluate the antigen specificity and phenotype of RSV F-specific B cells longitudinally after DS-Cav1 immunization. Peripheral blood mononuclear cells (PBMCs) collected at time points before the first immunization through the end of the trial at 44 weeks were assessed by flow cytometry. Our data demonstrate a rapid increase in the frequency of pre-F-specific IgG
CKS1 inhibition depletes leukemic stem cells and protects healthy hematopoietic stem cells in acute myeloid leukemia
Authors: William Grey, Ana Rio-Machin, Pedro Casado, Eva Grönroos, Sara Ali, Juho J. Miettinen, Findlay Bewicke-Copley, Alun Parsons, Caroline A. Heckman, Charles Swanton, Pedro R. Cutillas, John Gribben, Jude Fitzgibbon, Dominique Bonnet
Journal: Science Translational Medicine (2022)

Acute myeloid leukemia (AML) is an aggressive hematological disorder comprising a hierarchy of quiescent leukemic stem cells (LSCs) and proliferating blasts with limited self-renewal ability. AML has a dismal prognosis, with extremely low 2-year survival rates in the poorest cytogenetic risk patients, primarily due to the failure of intensive chemotherapy protocols to deplete LSCs and toxicity of therapy toward healthy hematopoietic cells. We studied the role of cyclin-dependent kinase regulatory subunit 1 (CKS1)–dependent protein degradation in primary human AML and healthy hematopoiesis xenograft models in vivo. Using a small-molecule inhibitor (CKS1i), we demonstrate a dual role for CKS1-dependent protein degradation in reducing patient-derived AML blasts in vivo and, importantly, depleting LSCs, whereas inhibition of CKS1 has the opposite effect on normal hematopoiesis, protecting normal hematopoietic stem cells from chemotherapeutic toxicity. Proteomic analysis of responses to CKS1i in our patient-derived xenograft mouse model demonstrate that inhibition of CKS1 in AML leads to hyperactivation of RAC1 and accumulation of lethal reactive oxygen species, whereas healthy hematopoietic cells enter quiescence in response to CKS1i, protecting hematopoietic stem cells. Together, these findings demonstrate that CKS1-dependent proteostasis is a key vulnerability in malignant stem cell biology.
Suvorexant ameliorated sleep disturbance, opioid withdrawal, and craving during a buprenorphine taper
Authors: Andrew S. Huhn, Patrick H. Finan, Charlene E. Gamaldo, Alexis S. Hammond, Annie Umbricht, Cecilia L. Bergeria, Eric C. Strain, Kelly E. Dunn
Journal: Science Translational Medicine (2022)

Increased orexin/hypocretin signaling is implicated in opioid withdrawal, sleep disturbances, and drug-seeking behaviors. This study examined whether a dual-orexin receptor antagonist would improve sleep and withdrawal outcomes when compared with placebo during a buprenorphine/naloxone taper. Thirty-eight participants with opioid use disorder were recruited to a clinical research unit and maintained on 8/2 to 16/4 mg of buprenorphine/naloxone treatment for 3 days before being randomized to 20 mg of suvorexant ( n = 14), 40 mg of suvorexant ( n = 12), or placebo ( n = 12); 26 individuals completed the study. After randomization, participants underwent a 4-day buprenorphine/naloxone taper and 4-day post-taper observation period. Total sleep time (TST) was collected nightly with a wireless electroencephalography device and wrist-worn actigraphy; opioid withdrawal symptoms were assessed via the Subjective Opiate Withdrawal Scale (SOWS); and abuse potential was assessed on a 0- to 100-point visual analog scale of “High” every morning. A priori outcomes included two-group (collapsing suvorexant doses versus placebo) and three-group comparisons of area-under-the-curve (AUC) scores for TST, SOWS, and High. In two-group comparisons, participants receiving suvorexant displayed increased TST during the buprenorphine/naloxone taper and decreased SOWS during the post-taper period. In three-group comparisons, participants receiving 20 mg of suvorexant versus placebo displayed increased AUC for TST during the buprenorphine/naloxone taper, but there was no difference in SOWS among groups. There was no evidence of abuse potential in two- or three-group analyses. The results suggest that suvorexant might be a promising treatment for sleep and opioid withdrawal in individuals undergoing a buprenorphine/naloxone taper.
Development and Validation of a Deep Learning Model to Screen for Trisomy 21 During the First Trimester From Nuchal Ultrasonographic Images
Authors: Liwen Zhang, Di Dong, Yongqing Sun, Chaoen Hu, Congxin Sun, Qingqing Wu, Jie Tian
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Accurate screening of trisomy 21 in the first trimester can provide an early opportunity for decision-making regarding reproductive choices. <h3>Objective</h3> To develop and validate a deep learning model for screening fetuses with trisomy 21 based on ultrasonographic images. <h3>Design, Setting, and Participants</h3> This diagnostic study used data from all available cases and controls enrolled at 2 hospitals in China between January 2009 and September 2020. Two-dimensional images of the midsagittal plane of the fetal face in singleton pregnancies with gestational age more than 11 weeks and less than 14 weeks were examined. Observers were blinded to subjective fetus nuchal translucency (NT) marker measurements. A convolutional neural network was developed to construct a deep learning model. Data augmentation was applied to generate more data. Different groups were randomly selected as training and validation sets to assess the robustness of the deep learning model. The fetal NT was shown and measured. Each detection of trisomy 21 was confirmed by chorionic villus sampling or amniocentesis. Data were analyzed from March 1, 2021, to January 3, 2022. <h3>Main Outcomes and Measures</h3> The primary outcome was detection of fetuses with trisomy 21. The receiver operating characteristic curve, metrics of accuracy, area under the curve (AUC), sensitivity, and specificity were used for model performance evaluation. <h3>Results</h3> A total of 822 case and control participants (mean [SD] age, 31.9 [4.6] years) were enrolled in the study, including 550 participants (mean [SD] age, 31.7 [4.7] years) in the training set and 272 participants (mean [SD] age, 32.3 [4.7] years) in the validation set. The deep learning model showed good performance for trisomy 21 screening in the training (AUC, 0.98; 95% CI, 0.97-0.99) and validation (AUC, 0.95; 95% CI, 0.93-0.98) sets. The deep learning model had better detective performance for fetuses with trisomy 21 than the model with NT marker and maternal age (training: AUC, 0.82; 95% CI, 0.77-0.86; validation: AUC, 0.73; 95% CI, 0.66-0.80). <h3>Conclusions and Relevance</h3> These findings suggest that this deep learning model accurately screened fetuses with trisomy 21, which indicates that the model is a potential tool to facilitate universal primary screening for trisomy 21.